During this past year we have worked with Dr. D'Argenio to design a trial for high dose Busulfan using stochastic control methods. Busulfan and cyclophosphamide administered as a high dose preparative regimen for bone marrow transplantation has been shown to be as effective as total body irradiation for selected pediatric malignant and non-malignant diseases. A major advantage of high dose chemotherapy regimens over radiation for children is avoiding the adverse effects of radiation on growth and development. However, there remain limitations to this commonly used therapy. The pharmacokinetics of both agents are highly variable and this variability can contribute to either low systemic exposures and insufficient myeloablation in the host to permit engraftment, or to high systemic exposure and severe toxicity. We have initiated a protocol to provide essential pharmacokinetic data for busulfan that will establish parenteral doses comparable to currently used oral therapy, demonstrate the ability to control for interpatient variability in pediatric patients, provide busulfan pharmacokinetic parameters for assessment of acceptable toxicity and efficacy, and determine possible differences in busulfan disposition in different pediatric patient populations. A central feature of this protocol is the ability to adjust doses of Busulfan in individual patients to target systemic exposure based on measured drug concentrations. This dose regimen design will be accomplished using the stochastic control approach developed by Dr. D'Argenio.